Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Here, we profiled the differential expression of miRNAs in circulating extracellular vesicles (EVs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes. METHODS: Circulating EV-associated miRNAs were investigated by use of an unbiased Taqman-based human miRNA array. Several EV miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in patients with aortic valve stenosis at day 7 after TAVR compared with the preprocedural levels in patients without LVEF improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day 7 (r=-0.264 and P=0.015) and 6 months (r=-0.328 and P=0.0018) after TAVR. RESULTS: Using of patient-derived samples and a murine aortic valve stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Mice with graded wire injury-induced aortic valve stenosis demonstrated a higher level of miR-122-5p, which was related to cardiomyocyte dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells compared with cardiomyocytes. Coculture experiments, copy-number analysis, and fluorescence microscopy with Cy3-labeled miR-122-5p demonstrated that miR-122-5p can be shuttled through large EVs from endothelial cells into cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes. Mechanistically, mass spectrometry, miRNA pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation experiments confirmed that miR-122-5p interacts with the RNA-binding protein hnRNPU (heterogeneous nuclear ribonucleoprotein U) in a sequence-specific manner to encapsulate miR-122-5p into large EVs. On shuttling, miR-122-5p reduces the expression of the antiapoptotic gene BCL2 by binding to its 3' untranslated region to inhibit its translation, thereby decreasing the viability of target cardiomyocytes. CONCLUSIONS: Increased levels of circulating proapoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR. EV shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a BCL2-dependent manner.

Sex Differences in Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Outcomes after transcatheter aortic valve replacement (TAVR) and infectious diseases may vary according to sex. METHODS: This multicentre study aimed to determine the sex differences in clinical characteristics, management, and outcomes of infective endocarditis (IE) after TAVR. A total of 579 patients (217 women, 37.5%) who had the diagnosis of definite IE following TAVR were included retrospectively from the Infectious Endocarditis After TAVR International Registry. RESULTS: Women were older (80 ± 8 vs 78 ± 8 years; P = 0.001) and exhibited a lower comorbidity burden. Clinical characteristics and microbiological profiles were similar between men and women, but culture-negative IE was more frequent in women (9.9% vs 4.3%; P = 0.009). A high proportion of patients had a clinical indication for surgery (54.4% in both groups; P = 0.99), but a surgical intervention was performed in a minority of patients (women 15.2%, men 20.3%; P = 0.13). The mortality rate at index IE hospitalisation was similar in both groups (women 35.4%, men 31.7%; P = 0.37), but women exhibited a higher mortality rate at 2-year follow-up (63% vs 52.1%; P = 0.021). Female sex remained an independent risk factor for cumulative mortality in the multivariable analysis (adjusted HR 1.28, 95% CI 1.02-1.62; P = 0.035). After adjustment for in-hospital events, surgery was not associated with better outcomes in women. CONCLUSIONS: There were no significant sex-related differences in the clinical characteristics and management of IE after TAVR. However, female sex was associated with increased 2-year mortality risk.

Percutaneous trans-axilla transcatheter aortic valve replacement.

The left axillary artery is an attractive alternative access route for transcatheter aortic valve replacement (TAVR) and may provide better outcomes compared to other alternatives. Nevertheless, there remain concerns about vascular complications, lack of compressibility, and thorax-related complications. Between March 2019 and March 2021, 13 patients underwent transaxillary TAVR for severe aortic stenosis at the University Hospital Bonn. The puncture was performed with a puncture at the distal segment of the axillary artery through the axilla, with additional femoral access for applying a safety wire inside the axillary artery. Device success was defined according to the VARC 2 criteria. The study participants were advanced in age (77 ± 9 years old), and 54% were female, with an intermediate risk for surgery (STS risk score 4.7 ± 2.0%). The average diameter of the distal segment of the axillary artery was 5.8 ± 1.0 mm (i.e., the puncture site) and 7.6 ± 0.9 mm for the proximal axillary artery. Device success was achieved in all patients. 30-day major adverse cardiac and cerebrovascular events were 0%. With complete percutaneous management, stent-graft implantation was performed at the puncture site in 38.5% of patients. Minor bleeding was successfully managed with manual compression. Moreover, no thorax-related complications, hematomas, or nerve injuries were observed. Percutaneous trans-axilla TAVR was found to be feasible and safe. This modified approach may mitigate the risk of bleeding and serious complications in the thorax and be less invasive than surgical alternatives.

Very early infective endocarditis after transcatheter aortic valve replacement.

BACKGROUND: Scarce data exist about early infective endocarditis (IE) after trans-catheter aortic valve replacement (TAVR). OBJECTIVE: The objective was to evaluate the characteristics, management, and outcomes of very early (VE) IE (≤ 30 days) after TAVR. METHODS: This multicenter study included a total of 579 patients from the Infectious Endocarditis after TAVR International Registry who had the diagnosis of definite IE following TAVR. RESULTS: Ninety-one patients (15.7%) had VE-IE. Factors associated with VE-IE (vs. delayed IE (D-IE)) were female gender (p = 0.047), the use of self-expanding valves (p < 0.001), stroke (p = 0.019), and sepsis (p < 0.001) after TAVR. Staphylococcus aureus was the main pathogen among VE-IE patients (35.2% vs. 22.7% in the D-IE group, p = 0.012), and 31.2% of Staphylococcus aureus infections in the VE-IE group were methicillin-resistant (vs. 14.3% in the D-IE group, p = 0.001). The second-most common germ was enterococci (34.1% vs. 24.4% in D-IE cases, p = 0.05). VE-IE was associated with very high in-hospital (44%) and 1-year (54%) mortality rates. Acute renal failure following TAVR (p = 0.001) and the presence of a non-enterococci pathogen (p < 0.001) were associated with an increased risk of death. CONCLUSION: A significant proportion of IE episodes following TAVR occurs within a few weeks following the procedure and are associated with dismal outcomes. Some baseline and TAVR procedural factors were associated with VE-IE, and Staphylococcus aureus and enterococci were the main causative pathogens. These results may help to select the more appropriate antibiotic prophylaxis in TAVR procedures and guide the initial antibiotic therapy in those cases with a clinical suspicion of IE. Very early infective endocarditis after trans-catheter aortic valve replacement. VE-IE indicates very early infective endocarditis (≤30 days post TAVR). D-IE indicates delayed infective endocarditis.

Surgical Treatment of Patients With Infective Endocarditis After Transcatheter Aortic Valve Implantation.

BACKGROUND: The optimal treatment of patients developing infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is uncertain. OBJECTIVES: The goal of this study was to investigate the clinical characteristics and outcomes of patients with TAVI-IE treated with cardiac surgery and antibiotics (IE-CS) compared with patients treated with antibiotics alone (IE-AB). METHODS: Crude and inverse probability of treatment weighting analyses were applied for the treatment effect of cardiac surgery vs medical therapy on 1-year all-cause mortality in patients with definite TAVI-IE. The study used data from the Infectious Endocarditis after TAVI International Registry. RESULTS: Among 584 patients, 111 patients (19%) were treated with IE-CS and 473 patients (81%) with IE-AB. Compared with IE-AB, IE-CS was not associated with a lower in-hospital mortality (HRunadj: 0.85; 95% CI: 0.58-1.25) and 1-year all-cause mortality (HRunadj: 0.88; 95% CI: 0.64-1.22) in the crude cohort. After adjusting for selection and immortal time bias, IE-CS compared with IE-AB was also not associated with lower mortality rates for in-hospital mortality (HRadj: 0.92; 95% CI: 0.80-1.05) and 1-year all-cause mortality (HRadj: 0.95; 95% CI: 0.84-1.07). Results remained similar when patients with and without TAVI prosthesis involvement were analyzed separately. Predictors for in-hospital and 1-year all-cause mortality included logistic EuroSCORE I, Staphylococcus aureus, acute renal failure, persistent bacteremia, and septic shock. CONCLUSIONS: In this registry, the majority of patients with TAVI-IE were treated with antibiotics alone. Cardiac surgery was not associated with an improved all-cause in-hospital or 1-year mortality. The high mortality of patients with TAVI-IE was strongly linked to patients' characteristics, pathogen, and IE-related complications.

Infective Endocarditis Caused by Staphylococcus aureus After Transcatheter Aortic Valve Replacement.

BACKGROUND: Staphylococcus aureus (SA) has been extensively studied as causative microorganism of surgical prosthetic-valve infective endocarditis (IE). However, scarce evidence exists on SA IE after transcatheter aortic valve replacement (TAVR). METHODS: Data were obtained from the Infectious Endocarditis After TAVR International Registry, including patients with definite IE after TAVR from 59 centres in 11 countries. Patients were divided into 2 groups according to microbiologic etiology: non-SA IE vs SA IE. RESULTS: SA IE was identified in 141 patients out of 573 (24.6%), methicillin-sensitive SA in most cases (115/141, 81.6%). Self-expanding valves were more common than balloon-expandable valves in patients presenting with early SA IE. Major bleeding and sepsis complicating TAVR, neurologic symptoms or systemic embolism at admission, and IE with cardiac device involvement (other than the TAVR prosthesis) were associated with SA IE (P < 0.05 for all). Among patients with IE after TAVR, the likelihood of SA IE increased from 19% in the absence of those risk factors to 84.6% if ≥ 3 risk factors were present. In-hospital (47.8% vs 26.9%; P < 0.001) and 2-year (71.5% vs 49.6%; P < 0.001) mortality rates were higher among patients with SA IE vs non-SA IE. Surgery at the time of index SA IE episode was associated with lower mortality at follow-up compared with medical therapy alone (adjusted hazard ratio 0.46, 95% CI 0.22-0.96; P = 0.038). CONCLUSIONS: SA IE represented approximately 25% of IE cases after TAVR and was associated with very high in-hospital and late mortality. The presence of some features determined a higher likelihood of SA IE and could help to orientate early antibiotic regimen selection. Surgery at index SA IE was associated with improved outcomes, and its role should be evaluated in future studies.

Perivalvular Extension of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Infective endocarditis (IE) following transcatheter aortic valve replacement (TAVR) has been associated with a dismal prognosis. However, scarce data exist on IE perivalvular extension (PEE) in such patients. METHODS: This multicenter study included 579 patients who had the diagnosis of definite IE at a median of 171 (53-421) days following TAVR. PEE was defined as the presence of an intracardiac abscess, pseudoaneurysm, or fistula. RESULTS: A total of 105 patients (18.1%) were diagnosed with PEE (perivalvular abscess, pseudoaneurysm, fistula, or a combination in 87, 7, 7, and 4 patients, respectively). A history of chronic kidney disease (adjusted odds ratio [ORadj], 2.08; 95% confidence interval [CI]: 1.27-3.41; P = .003) and IE secondary to coagulase-negative staphylococci (ORadj, 2.71; 95% CI: 1.57-4.69; P < .001) were associated with an increased risk of PEE. Surgery was performed at index IE episode in 34 patients (32.4%) with PEE (vs 15.2% in patients without PEE, P < .001). In-hospital and 2-year mortality rates among PEE-IE patients were 36.5% and 69.4%, respectively. Factors independently associated with an increased mortality were the occurrence of other complications (stroke post-TAVR, acute renal failure, septic shock) and the lack of surgery at index IE hospitalization (padj < 0.05 for all). CONCLUSIONS: PEE occurred in about one-fifth of IE post-TAVR patients, with the presence of coagulase-negative staphylococci and chronic kidney disease determining an increased risk. Patients with PEE-IE exhibited high early and late mortality rates, and surgery during IE hospitalization seemed to be associated with better outcomes.

Transcatheter aortic valve implantation in patients with a small aortic annulus: performance of supra-, intra- and infra-annular transcatheter heart valves.

BACKGROUND: A small aortic annulus is associated with increased risk of prosthesis-patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI). Whether specific transcatheter heart valve (THV) designs yield superior hemodynamic performance in these small anatomies remains unclear. METHODS: Data from 8411 consecutive patients treated with TAVI from May 2012 to April 2019 at four German centers were retrospectively evaluated. A small aortic annulus was defined as multidetector computed tomography-derived annulus area < 400 mm2. TAVI was performed with a balloon-expanding intra-annular (Sapien-3, n = 288), self-expanding intra-annular (Portico, n = 110), self-expanding supra-annular (Evolut, n = 179 and Acurate-Neo, n = 428) and mechanically expanding infra-annular (Lotus, n = 64) THV according to local practice. PPM was defined as indexed effective orifice area ≤ 0.85cm2/m2. RESULTS: A small annulus was found in 1069 (12.7%) patients. PPM was detected in 38.3% overall with a higher prevalence after implantation of a balloon-expanding intra-annular or mechanically expanding infra-annular THV compared to self-expanding intra- and supra-annular THV. Multivariable analysis linked self-expanding THV (Evolut: Odds ratio [OR] 0.341, Acurate-Neo: OR 0.436, Portico: OR 0.291), postdilatation (OR 0.648) and age (OR 0.968) to lower rates of PPM, while aortic valve calcification was associated with an increased risk (OR 1.001). Paravalvular regurgitation > mild was more frequent after TAVI with self-expanding THV (p = 0.04). CONCLUSION: In this large contemporary multicenter patient population, a substantial number of patients with a small aortic anatomy were left with PPM after TAVI. Self-expanding supra- and intra-annular THV demonstrated superior hemodynamics in these patients at risk, however at the cost of higher rates of residual paravalvular regurgitation.

Frailty in patients undergoing transcatheter aortic valve replacement: prognostic value of the Geriatric Nutritional Risk Index.

BACKGROUND: Malnutrition is a hallmark of frailty, is common among elderly patients, and is a predictor of poor outcomes in patients with severe symptomatic aortic stenosis (AS). The Geriatric Nutritional Risk Index (GNRI) is a simple and well-established screening tool to predict the risk of morbidity and mortality in elderly patients. In this study, we evaluated whether GNRI may be used in the risk stratification and management of patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Patients with symptomatic severe AS (n = 953) who underwent transfemoral TAVR at the University Hospital Schleswig-Holstein Kiel, Germany, between 2010 and 2019 (development cohort) were divided into two groups: normal GNRI ≥ 98 (no nutrition-related risk; n = 618) versus low GNRI < 98 (at nutrition-related risk; n = 335). The results were validated in an independent (validation) cohort from another high-volume TAVR centre (n = 977). RESULTS: The low-GNRI group had a higher proportion of female patients (59.1% vs. 52.1%), higher median age (82.9 vs. 81.8 years), prevalence of atrial fibrillation (50.4% vs. 40.0%), median logistic EuroSCORE (17.5% vs. 15.0%) and impaired left ventricular function (<35%: 10.7% vs. 6.8%), lower median estimated glomerular filtration rate (50 vs. 57 mL/min/1.73 m2 ) and median albumin level (3.5 vs. 4.0 g/dL) compared with the normal-GNRI group. Among peri-procedural complications, Acute Kidney Injury Network (AKIN) Stage 3 was more common in the low-GNRI group (3.6% vs. 0.6%, p = 0.002). After a mean follow-up of 21.1 months, all-cause mortality was significantly increased in the low-GNRI group compared with the normal-GNRI group (p < 0.001). This was confirmed in the validation cohort (p < 0.001). Low GNRI < 98 was identified as an independent risk factor for all-cause mortality (hazard ratio 1.44, 95% CI 1.01-2.04, p = 0.043). Other independent risk factors included albumin level < median of 4.0 g/dL, high-sensitive troponin T in the highest quartile (> 45.0 pg/mL), N-terminal pro-B-type natriuretic peptide in the highest quartile (> 3595 pg/mL), grade III-IV tricuspid regurgitation, pulmonary arterial hypertension, life-threatening bleeding, AKIN Stage 3 and disabling stroke. CONCLUSIONS: Low GNRI score was associated with an increased risk of all-cause mortality in patients undergoing TAVR, implying that this vulnerable group may benefit from improved preventive measures.

Transcatheter Replacement of Transcatheter Versus Surgically Implanted Aortic Valve Bioprostheses.

BACKGROUND: Surgical aortic valve replacement and transcatheter aortic valve replacement (TAVR) are now both used to treat aortic stenosis in patients in whom life expectancy may exceed valve durability. The choice of initial bioprosthesis should therefore consider the relative safety and efficacy of potential subsequent interventions. OBJECTIVES: The aim of this study was to compare TAVR in failed transcatheter aortic valves (TAVs) versus surgical aortic valves (SAVs). METHODS: Data were collected on 434 TAV-in-TAV and 624 TAV-in-SAV consecutive procedures performed at centers participating in the Redo-TAVR international registry. Propensity score matching was applied, and 330 matched (165:165) patients were analyzed. Principal endpoints were procedural success, procedural safety, and mortality at 30 days and 1 year. RESULTS: For TAV-in-TAV versus TAV-in-SAV, procedural success was observed in 120 (72.7%) versus 103 (62.4%) patients (p = 0.045), driven by a numerically lower frequency of residual high valve gradient (p = 0.095), ectopic valve deployment (p = 0.081), coronary obstruction (p = 0.091), and conversion to open heart surgery (p = 0.082). Procedural safety was achieved in 116 (70.3%) versus 119 (72.1%) patients (p = 0.715). Mortality at 30 days was 5 (3%) after TAV-in-TAV and 7 (4.4%) after TAV-in-SAV (p = 0.570). At 1 year, mortality was 12 (11.9%) and 10 (10.2%), respectively (p = 0.633). Aortic valve area was larger (1.55 ± 0.5 cm2 vs. 1.37 ± 0.5 cm2; p = 0.040), and the mean residual gradient was lower (12.6 ± 5.2 mm Hg vs. 14.9 ± 5.2 mm Hg; p = 0.011) after TAV-in-TAV. The rate of moderate or greater residual aortic regurgitation was similar, but mild aortic regurgitation was more frequent after TAV-in-TAV (p = 0.003). CONCLUSIONS: In propensity score-matched cohorts of TAV-in-TAV versus TAV-in-SAV patients, TAV-in-TAV was associated with higher procedural success and similar procedural safety or mortality.

Impact of cancer history on clinical outcome in patients undergoing transcatheter edge-to-edge mitral repair.

BACKGROUND: Little is known about the prevalence of a history of cancer and its impact on clinical outcome in mitral regurgitation (MR) patients undergoing transcatheter mitral valve repair (TMVR). OBJECTIVES: The purpose of this study is to investigate the prevalence of cancer, baseline inflammatory parameters, and clinical outcome in MR patients undergoing TMVR. METHODS: Consecutive patients undergoing a MitraClip procedure were enrolled, and the patients were stratified into two groups: cancer and non-cancer. Baseline complete blood counts (CBC) with differential hemograms were collected prior to the procedure to calculate the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). All-cause death within a one-year was examined. RESULTS: In total, 82 out of 446 patients (18.4%) had a history of cancer. Cancer patients had a significantly higher baseline PLR [181.4 (121.1-263.9) vs. 155.4 (109.4-210.4); P = 0.012] and NLR [5.4 (3.5-8.3) vs. 4.0 (2.9-6.1); P = 0.002] than non-cancer patients. A Kaplan-Meier analysis revealed that cancer patients had a significantly worse prognosis than non-cancer (estimated 1-year mortality, 20.2 vs. 9.2%; log-rank P = 0.009), and multivariable analyses of three models showed that cancer history was an independent factor for 1-year mortality. Patients who died during follow-up had a significantly higher baseline PLR [214.2 (124.2-296.7) vs. 156.3 (110.2-212.1); P = 0.007] and NLR [6.4 (4.2-12.5) vs. 4.0 (2.9-6.2); P < 0.001] than survivors. CONCLUSIONS: In MitraClip patients, a history of cancer was associated with higher inflammatory parameters and worse prognosis compared to non-cancer patients. Central Illustration. Clinical outcomes and baseline PLR and NLR values accord-ing to one-year mortality. (Left) Patients who died within the follow-up period had a significantly higher baseline PLR (214.2 [124.2-296.7] vs 156.3 [110.2-212.1]; P = 0.007) and NLR (6.4 [4.2-12.5] vs 4.0 [2.9-6.2]; P < 0.001) than patients who survived. PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio (Right) A Kaplan-Meier analysis revealed that cancer patients had a significantly worse prognosis than non-cancer patients (estimated one-year mortality, 20.2 vs 9.2%; log-rank P = 0.009).

Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. METHODS: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. RESULTS: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76-996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510-1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR (P<0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients (P=0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P<0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P=0.02). The rates of Mitral Valve Academic Research Consortium-defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P=0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74-12.56; P=0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88-21.53; P<0.001) were both independently associated with repeat mitral valve replacement. CONCLUSIONS: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

Impact of Coronary Artery Disease on Outcomes in Patients Undergoing Percutaneous Edge-to-Edge Repair.

OBJECTIVES: The aim of this observational study was to evaluate the impact of concomitant coronary artery disease (CAD) on outcomes in patients undergoing percutaneous valve repair with the MitraClip system. BACKGROUND: Mitral valve regurgitation and CAD are often coexistent in elderly patients undergoing percutaneous mitral valve repair. The impact of CAD and revascularization on outcomes in this patient cohort, however, remains uncertain. METHODS: In 444 MitraClip patients, CAD severity was assessed, represented by the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS), as well as the residual SS (rSS) and SYNTAX score II (SS-II). Patients were stratified according to CAD severity and SS-II values (SS ≤3 vs. SS >3 and SS-II ≤45 vs. SS-II >45) and according to remaining CAD burden into 2 groups (rSS = 0 vs. rSS >0) to compare 1-year all-cause mortality. RESULTS: Higher SS, rSS, and SS-II were associated with mortality (22% for SS >3 vs. 9.6% for SS ≤3 [p < 0.001], 31.4% for rSS >0 vs. 9.6% for rSS = 0 [p < 0.001], and 17.1% for SS-II > 45 vs. 11.2% for SS-II ≤45 [p = 0.044]). The rSS was an independent predictor of 1-year all-cause mortality (p = 0.001) in multivariate analysis. CONCLUSIONS: The complexity of CAD, as assessed using the SS, is associated with outcomes in patients undergoing MitraClip procedures. The burden of residual CAD after percutaneous coronary intervention is an independent predictor of 1-year all-cause mortality. Patients undergoing complete revascularization had the most favorable outcomes independent of mitral regurgitation etiology.

Prognostic Impact of Redo Transcatheter Mitral Valve Repair for Recurrent Mitral Regurgitation.

There is little known about the prognostic impact of a redo transcatheter mitral valve repair (TMVR) for residual or recurrent mitral regurgitation (MR). From January 2011 to March 2019, we identified 43 consecutive patients who underwent a redo TMVR procedure with the MitraClip system. A control cohort was treated medically for MR ≥2+ after the first TMVR and was propensity score 1:1 matched using age, gender, MR severity, trans-mitral pressure gradient, and etiology of MR. To investigate the association of redo TMVR with 1-year mortality, we fitted a Cox proportional hazard model. The technical success rate of redo TMVR was 95%. A reduction in MR to ≤2+ was achieved in 79% of patients, with a significant decline of tricuspid regurgitation pressure gradient and improvement of the New York Heart Association class. After matching was performed, 43 well-matched pairs of patients were analyzed. Redo TMVR patients showed lower 1-year mortality (10.5% vs 37.6%, p = 0.01) compared with the control patients. Redo TMVR was associated with better survival (hazard ratio [HR] 0.26, 95% confidence interval [CI] 0.08 to 0.79, p = 0.02) and lower risk of the composite end point (mortality and rehospitalization due to HF: HR 0.34, 95% CI 0.15 to 0.78; p = 0.01) at 1-year follow-up. The association with the primary end point remained significant after accounting for the New York Heart Association class III/IV, TR ≥severe, the type of MR (i.e., recurrent or residual MR), or the type of previous implanted TMVR device. In conclusion, redo TMVR in selected patients with residual or recurrent MR may be associated with lower 1-year mortality than medical therapy alone.

Repeat Transcatheter Aortic Valve Replacement for Transcatheter Prosthesis Dysfunction.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) use is increasing in patients with longer life expectancy, yet robust data on the durability of transcatheter heart valves (THVs) are limited. Redo-TAVR may play a key strategy in treating patients in whom THVs fail. OBJECTIVES: The authors sought to examine outcomes following redo-TAVR. METHODS: The Redo-TAVR registry collected data on consecutive patients who underwent redo-TAVR at 37 centers. Patients were classified as probable TAVR failure or probable THV failure if they presented within or beyond 1 year of their index TAVR, respectively. RESULTS: Among 63,876 TAVR procedures, 212 consecutive redo-TAVR procedures were identified (0.33%): 74 within and 138 beyond 1 year of the initial procedure. For these 2 groups, TAVR-to-redo-TAVR time was 68 (38 to 154) days and 5 (3 to 6) years. The indication for redo-TAVR was THV stenosis in 12 (16.2%) and 51 (37.0%) (p = 0.002) and regurgitation or combined stenosis-regurgitation in 62 (83.8%) and 86 (62.3%) (p = 0.028), respectively. Device success using VARC-2 criteria was achieved in 180 patients (85.1%); most failures were attributable to high residual gradients (14.1%) or regurgitation (8.9%). At 30-day and 1-year follow-up, residual gradients were 12.6 ± 7.5 mm Hg and 12.9 ± 9.0 mm Hg; valve area 1.63 ± 0.61 cm2 and 1.51 ± 0.57 cm2; and regurgitation ≤mild in 91% and 91%, respectively. Peri-procedural complication rates were low (3 stroke [1.4%], 7 valve malposition [3.3%], 2 coronary obstruction [0.9%], 20 new permanent pacemaker [9.6%], no mortality), and symptomatic improvement was substantial. Survival at 30 days was 94.6% and 98.5% (p = 0.101) and 83.6% and 88.3% (p = 0.335) at 1 year for patients presenting with early and late valve dysfunction, respectively. CONCLUSIONS: Redo-TAVR is a relatively safe and effective option for selected patients with valve dysfunction after TAVR. These results are important for applicability of TAVR in patients with long life expectancy in whom THV durability may be a concern.

Prognostic impact of cancer history in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: The benefit of TAVI in cancer patients is currently unclear. OBJECTIVES: The purpose of this study is to investigate prognostic impact of cancer status (active cancer or previous cancer) in severe aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: Consecutive TAVI patients in the Heart Center Bonn were enrolled and we stratified the patients into three groups: current cancer (active cancer), non-current cancer (previous cancer), or no cancer. The primary outcome was all-cause death within a 5-year follow-up. We evaluated mean aortic pressure gradient (mPG) values following TAVI (baseline mPG) and at the final follow-up (follow-up mPG). RESULTS: In total, 1568 TAVI patients were eligible and 298 patients (19.0%) had active or previous cancer. At the 5-year follow-up, cancer patients had a significantly worse prognosis than non-cancer patients (log rank, P < 0.001). In a multivariable analysis, previous cancer was a significant predictor for 5-year mortality (hazard ratio [HR], 1.56; P < 0.001). Estimated mortality rates at 5-year follow-up rates among active cancer, previous cancer, and non-cancer were 84.0%, 65.8%, and 50.2% (long-rank P < 0.001), respectively. The hazard ratios of active cancer and previous cancer for 5-year mortality were 2.79 (P < 0.001) and 1.38 (P = 0.019) compared to non-cancer patients. We found significantly higher mPG during follow-up than at baseline in cancer patients (follow-up 8.10 vs baseline 7.40 mmHg; Wilcoxon P = 0.012). CONCLUSIONS: Active, and also previous, cancer status are associated with less beneficial long-term prognosis in TAVI patients.

Predictive factors and long-term prognosis of transcatheter aortic valve implantation-associated endocarditis.

BACKGROUND: There are still limited data regarding transcatheter aortic valve implantation (TAVI) endocarditis. OBJECTIVES: The objective of the present study was to investigate the predictor and long-term outcome of TAVI endocarditis. METHODS: Consecutive patients undergoing TAVI at the University of Bonn were prospectively enrolled in this study. Transcatheter heart valve (THV) endocarditis was defined according to Duke criteria. The primary outcome was all-cause death within a 5-year follow-up. RESULTS: 1448 successful TAVI patients were eligible for the study and 17 patients (1.2%) developed THV endocarditis during the follow-up period (median 294 days). A multivariable logistic regression analysis identified age (odds ratio [OR] 0.90; P = 0.001) and residual paravalvular leakage (PVL) ≥ 2 after TAVI (OR 5.15; P = 0.015) as the main predictors for the occurrence of TAVI endocarditis. Additional analyses revealed that younger patients were significantly associated with higher rates of diabetes (P = 0.001), hemodialysis (P < 0.001), prior cardiac surgery (P < 0.001), and chronic obstructive pulmonary disease (COPD) (P < 0.001). A Kaplan-Meier analysis showed a significantly worse prognosis in TAVI patients with endocarditis than in patients without (log-rank; P = 0.03) during the 5-year follow-up. A multivariable Cox proportional hazard analysis revealed that TAVI endocarditis is an independent predictor of long-term mortality (hazard ratio 4.17; 95% CI 1.91-9.07; P < 0.001). CONCLUSIONS: Our study identified lower age and residual PVL ≥ 2 as predictors for THV endocarditis, which itself may be considered as an independent predictor of long-term mortality after TAVI.

Surgical Revascularization of Chronically Occluded Coronary Arteries-What You See Is What You Get?

BACKGROUND: Revascularization strategy in coronary artery bypass grafting (CABG) surgery usually depends on coronary dimension and stenosis severity. Little is known about the relation of preoperative evaluation of scarcely or invisibly chronic occluded coronary arteries (chronic total occlusion [CTO]) and revascularization rate or anastomosis quality. We aimed to evaluate the success rates of CTO revascularization in CABG surgery and determine the influence of coronary lumen visibility and collateralization in preoperative angiograms on revascularization rates, bypass blood flow, and target vessel diameter. METHOD: Preoperative coronary angiograms were evaluated for 938 consecutive patients who underwent isolated CABG surgery between 2014 and 2016 and screened for occluded coronary arteries. The occluded vessels were scored for visibility using the Rentrop grading of collateral filling. Intraoperatively, dimensions of the occluded arteries were measured using conventional vessel probes, and anastomosis quality was assessed by transit time flow measurement. RESULTS: A total of 404 (43.1%) patients were identified with at least one CTO. Revascularization rates differed from 96.2% in the left anterior descending artery, to 85.0% in left circumflex artery-dependent vessels, and 78.8% in right coronary artery territory. Coronary visibility and grade of collateralization in the preoperative angiogram had no influence on intraoperatively measured coronary diameter. Bypass blood flow in grafts revascularizing CTOs lacking collateralization were not significantly lower than those grafts leading to CTOs with higher Rentrop scores. CONCLUSION: Preoperative coronary assessment often differs from intraoperative findings. Our study confirms that even patients with scarcely collateralized CTOs and impaired visibility in the coronary angiogram have a high chance of complete revascularization during CABG surgery.

Six months follow-up of protected high-risk percutaneous coronary intervention with the microaxial Impella pump: results from the German Impella registry.

BACKGROUND: Percutaneous coronary intervention (PCI) represents an important alternative to coronary bypass surgery for the treatment of patients with complex coronary artery disease and high perioperative risk. Protected percutaneous coronary intervention applies temporary percutaneous ventricular assist devices to mitigate potential hemodynamic compromise in high-risk patients. The Impella system is currently the most commonly used device for protected percutaneous coronary intervention and showed improved hemodynamic parameters in earlier trials. METHODS: This study was designed as a retrospective, observational multi-center registry conducted in ten hospitals in Germany. We included consecutive patients undergoing protected high-risk percutaneous coronary intervention with Impella support. The primary endpoint was defined as the occurrence of a major adverse cardiac event defined as all-cause mortality, ST-elevation myocardial infarction, or stroke during a postprocedural 180-day follow-up period. RESULTS: In total, 157 patients (80.3% male; mean age 71.8 ± 10.8 years) were included in the present study, and 180-day follow-up was complete for 149 patients (94.9%). At baseline, the patients had a median left ventricular ejection fraction of 39.0% (interquartile range, 25.0-50.0%). The median SYNergy between PCI with TAXUS and Cardiac Surgery-Score I was 33.0 (interquartile range, 24.0-40.5) and the median EuroSCORE II was 7.2% (interquartile range, 3.2-17.1%). During postprocedural follow-up, 34 patients (22.8%) suffered a major adverse cardiac event. All-cause mortality was 18.1% (27 patients). Nine patients (6.0%) sustained a ST-elevation myocardial infarction, while 4 patients (2.7%) had a stroke. CONCLUSIONS: Patients undergoing protected high-risk percutaneous coronary intervention with Impella support showed an acceptable 180-day clinical outcome regarding major adverse cardiac event and mortality.